A frequency‐selective pH‐responsive paraCEST agent
2020
Extracellular pH is an important biomarker in many diseases yet a routine method for imaging tissue pH has not been established in the clinic. Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well-suited for imaging tissue pH because the basis of CEST, chemical exchange, is inherently sensitive to pH. Several previous pH-sensitive paraCEST agents were based upon with an exchanging Ln 3+ bound water molecule as the CEST antenna but this design often added additional line-broadening of the bulk water signal due to T 2 exchange. We report here a pH-sensitive paraCEST agent that lacks an inner-sphere water molecule but contains one Ln-bound -OH group for CEST activation. The Yb 3+ - complex, Yb( 1 ), displayed a single, highly-shifted CEST peak originating from the exchangeable Yb-OH proton, the frequency of which changed over the biologically relevant pH range. CEST images of phantoms ranging in pH from 6-8 demonstrate the potential of this agent for imaging pH. Initial rodent imaging studies showed that Gd( 1 ) remains in the vascular system much longer than anticipated but is cleared slowing via renal filtration.
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